The underlying hepatoprotective mechanism of PKC#963 in alcohol or carbon tetrachloride induced liver injury via inhibition of iNOS, COX‐2, and p‐STAT3 and enhancement of SOD and catalase

The aim of the present study is to explore the underlying hepatoprotective mechanism of PKC#963, consisting of Pinus koraiensis, Saururus chinensis, and Lycium barbarum in association with acute and chronic liver injury induced by alcohol or carbon tetrachloride (CCl4). Here, PKC#963 significantly suppressed aspartate aminotransferase (AST), alanine aminotransferase (ALT), phosphorylated signal transducer and activator of transcription 3 (p-STAT3), inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2) in CCl4-treated HepG2 cells. Also, PKC#963 significantly suppressed reactive oxygen species (ROS) production in HepG2 cells. Consistently, PKC#963 suppressed the expression of AST, ALT, p-STAT3, iNOS, COX-2, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α) and α-smooth muscle actin (α-SMA) and increased procaspase 3 in the liver tissues of CCl4 treated rats. In addition, PKC#963 enhanced alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) for alcohol metabolism, superoxide dismutase (SOD), and catalase as antioxidant enzymes and also suppressed AST and ALT in alcohol-treated rats. Furthermore, PKC#963 reduced hepatic steatosis and necrosis in CCl4-treated rats by H&E (Hematoxylin and Eosin) staining. Taken together, these findings highlight evidence that PKC#963 has hepatoprotective potential via inhibition of iNOS, COX-2, and p-STAT3 and enhancement of SOD and catalase.